. This investigation has as its goal, the design, synthesis and biological evaluation of a series of thionucleoside analogs of oxetanocin (OXT-A) and other related compounds as potential antiviral, particularly anti-HIV-1, anti-CMV, and anti-HBV agents. If these analogs are phosphorylated by cellular kinases to the respective nucleotides, which have the ability to interfere selectively with the viral or cancer DNA synthesis or being incorporated into DNA, then they could become useful antiviral and/or anticancer agents for chemotherapy. In addition, several 4,6-diamino-5- nitropyrimidine nucleoside analogs of oxetanocin will be synthesized and biologically evaluated in vitro for their activity against HIV, HBV, CMV, and other viruses. In these compounds, the 4,6-diamino-5-nitropyrimidine mimics the adenine base in oxetanocin. Various natural and synthetic cytosine nucleosides such as 1-B-D-arabinofuranosylcytosine (ara-C) and 1-(2-fluoro-2-deoxy-Beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) have been shown to possess potent anticancer and antiviral activity, respectively. However, many of these biologically active cytosine nucleosides either have a therapeutic index that is too low for human use or their anticancer and/or antiviral efficacies are diminished by their susceptibility to rapid deamination to inactive uracil nucleoside analogs. In order to circumvent these problems, the investigators propose to synthesize and evaluate a series of 2'-ethynyl, 2'-ethenyl, 2'-hydroxymethyl, 2'-fluoromethyl, 2'-azidomethyl, and 2'-aminomethyl analogs of ara-C and related compounds. These compounds will be screened primarily for anticancer activity. However, those compounds in this series, found to be non-cytotoxic or much less toxic than ara-C will be tested and developed as potential antiviral agents. The approaches to be employed in this proposal include the development of methodology for the synthesis of these nucleoside analogs, their characterization by NMR, mass spectrum, UV, and other spectroscopic techniques, and the determination of their biological and biochemical effects.